There is increasing evidence to support the hypothesis that somatic cell mutations are causally related to chemical and physical carcinogenesis and that cellular DNA repair processes recognize and repair lesions in DNA caused by the attack of carcinogens. We have recently reported that the frequency of mutations induced in cells derived from xeroderma pigmentosum (XP) patients (who are prone to sunlight-induced skin cancer and defective in excision repair or post-replication repair of UV light-induced DNA damage) is significantly higher than in normal human cells. Our preliminary studies suggest that a similar result occurs with carcinogenic hydrocarbon derivatives as the DNA-damaging agents. Although studies have been done to detect, characterize, and quantitate DNA repair following carcinogen attack, few have directly examined the effect of DNA repair processes on the induction of mutations and correlated this with the number and types of DNA adducts formed. The fundamental purpose of this research is to examine the effect of DNA repair on the induction of mutations by selected carcinogenic agents in normal human cells and in cells derived from persons with genetic predisposition to cancer (classical and variant XP's; ataxia telangiectasia; Fanconi's anemia; etc.). We will: 1) investigate the effect of DNA excision repair processes acting on chemical agents induce "UV-like" repair, "gamma-ray-like" repair, cross-links, etc; 2) determine the effect of DNA post-replication repair of such damage; and 3) determine, using radioactively-labeled carcinogens and sensitive biochemical techniques, the number and kinds of DNA-carcinogen adducts that correlate with the induction of mutations in these cells. As a corollary, we will: 4) compare the effects of "simulated sunlight" with those found for 254 nm; and 5) compare the effects of carcinogens in human epithelial cells with those observed in fibroblasts.